Diesel Exhaust Linked to Cancer Development Through Blood Vessel Growth

Lung Chi Chen, Ph.D. and Qinghua Sun, MD, Ph.D.,
New York University School of Medicine and Ohio State University
NIEHS Grants P30ES000260, R01ES015495, and K01ES016588

NIEHS-supported scientists have determined a way that exposure to diesel exhaust stimulates the growth of cancerous tumors. Using a laboratory mouse research model, the research team from New York University and Ohio State University determined that exposure to diesel exhaust particles stimulates the growth and formation of new blood vessels necessary for solid tumors to grow. The studies were carried out at exposure levels similar to those found in urban areas with heavy commuting traffic and were lower than levels typically encountered by workers using diesel-powered equipment.

Inhaled diesel exhaust particles are mostly less than 0.1 micrometers in diameter, which enables them to penetrate the circulatory system and other organs, and allows them to cause damage in just about any tissue in the body.

The researchers employed a two-prong research approach. First they implanted small platforms embedded with normal endothelial cells, the cells that line blood vessels, under the skin of healthy mice. In another set of mice, the researchers surgically created an ischemic condition in the hind limbs. Ischemia causes hypoxia, which is a severe lack of oxygen, and a condition seen in certain diseases. Mice from both groups were assigned to breathe either filtered outdoor air or air contaminated with diesel exhaust particles for 6 hours per day. The rest of time the animals breathed filtered air.

Effects were seen beginning after just two-weeks of exposure, but the longer the experiment was continued the more severe the effect. Exposure to diesel exhaust caused a six-fold increase in new blood vessel formation in the ischemic limbs at eight weeks and a four-fold increase in the non-ischemic limbs compared to the mice breathing normal air.

Similar effects were seen in the mice with the implanted cells. The researchers found three types of blood vessel development; the development of new capillaries, re-started growth of existing blood vessels, and the formation of new vessels. All of these processes are needed for solid tumor growth.

The team conducted additional studies to try to determine the mechanism behind the vascular changes. They found that exposure to diesel particles activates vascular endothelial growth factor, a chemical signal associated with new blood vessel development. They also found that a blood vessel growth factor is activated by diesel exposure and lowered activity for an enzyme involved in tumor suppression. The researchers are now conducting experiments to determine whether exposure to diesel exhaust influences metastasis of tumors as well.

Citation: Xu X, Kherada N, Hong X, Quan C, Zheng L, Wang A, Wold L, Lippmann M, Chen LC, Rajagopalan S, Sun Q. Diesel exhaust exposure induces angiogenesis. Toxicol Lett. 2009 Aug 14.